Rapid Access to Acylation and Alkylation of N-Heteroarenes Using Ester Acetates as Reactants

Abstract

The laboratory-abundant and low-toxic ethyl acetate was explored successfully for the first time as acyl group donor for the Minisci-type acylation of quinolines. In this approach, TBAC/K₂S₂O₈ (TBAC: tert-butylacetyl chloride) system played a important role, and the introduced acyl group was derived from the alkoxyl group moiety of ester acetates. Most N-heteroarenes, such as quinoxaline and isoquinoline, etc. were also compatible to this synthetic strategy affording acylated products in high yields. Simultaneously, the C2—H alkylation was realized by accident for 4-quinazolinone. Furthermore, the acylation mechanism was proposed through the chlorine radical abstracting the inactive α-hydrogen of the alkoxyl group.

Keywords

Ethyl acetate / Acylation / Chlorine radical / N-Heteroarene / Minisci-type

References

[1] Zhao M, Zhang K, Xu J, Li J. Org. Chem. Front., 2022, 9: 4063

[2] Ambala S, Thatikonda T, Sharma S, Munagala G, Yempalla K R, Vishwakarma R A, Singh P P. Org. Biomol. Chem., 2015, 13: 11341

[3] Jukic M, Sterk D, Casar Z. Curr. Org. Synth., 2012, 9: 488

[4] Talukdar R. Org. Biomol. Chem., 2020, 18: 8876

[5] Li F. Chem. Res. Chinese Universities, 2023, 39: 159

[6] Guo A, Han J B, Zhu L, Wei Y, Tang X Y. Org. Lett., 2019, 21: 2927

[7] Yu J T, Li Y, Chen R, Yang Z, Pan C. Org. Biomol. Chem., 2021, 19: 4520

[8] Proctor R S J, Phipps R J. Angew. Chem. Int. Ed., 2019, 58: 13666

[9] Wang W, Wang S. Curr. Org. Chem., 2021, 25: 894

[10] Gyorfi N, Kotschy A, Gyuris M. Eur. J. Org. Chem., 2020, 2020: 6447

[11] Wang C, Shi H, Deng G J, Huang H. Org. Biomol. Chem., 2021, 19: 9177

[12] Itabashi Y, Asahara H, Ohkubo K. Chem. Commun., 2023, 59: 7506

[13] Kariofillis S K, Doyle A G. Acc. Chem. Res., 2021, 54: 988

[14] Zhang K, Xu J, Xiao J, Zhong R, Li J. Eur. J. Org. Chem., 2023, 26: e202201432

[15] Wen C, Zhong R, Qin Z, Zhao M, Li J. Chem. Commun., 2020, 56: 9529

[16] Zhang Y, Wen C, Li J. Org. Biomol. Chem., 2018, 16: 1912

[17] Yuan J W, Fu J H, Liu S N, Xiao Y M, Mao P, Qu L B. Org. Biomol. Chem., 2018, 16: 3203

[18] Nakao Y, Idei H, Kanyiva K S, Hiyama T. J. Am. Chem. Soc., 2009, 131: 15996

[19] Neises B, Steglich W. Angew. Chem. Int. Ed., 1978, 17: 522

[20] Jiang H, Xie J, Lin A, Cheng Y, Zhu C. Rsc. Adv., 2012, 2: 10496

[21] Mamedov V A, Kalinin A A, Gubaidullin A T, Isaikina O G, Litvinov I A. Russ. J. Org. Chem., 2005, 41: 599

[22] Kudale V S, Mutra M R, Chu C P, Wang J J. Org. Biomol. Chem., 2021, 19: 5567

[23] Chen J, Wan M, Hua J, Sun Y, Lv Z, Li W, Liu L. Org. Biomol. Chem., 2015, 13: 11561

[24] Kostakis I K, Elomri A, Seguin E, Iannelli M, Besson T. Tetrahedron Lett., 2007, 48: 6609